The objectives of this pilot project are to establish the source of infection in SIV-infected monkeys, characterize immune correlates of disease, and determine the feasibility of vaccination to prevent opportunistic infection of SAIDS animals with Mycobacterium avium. The incidence of M. avium infection (MAI) in the SAIDS colony has increased from undetectable levels in 1988 to 18-25% in recent years. This opportunistic infection produces diarrhea, cachexia, and sometimes pneumonia in severely immunocompromized monkeys with remarkable similarity to MAI in children with AIDS. We detect M. avium by culture and PCR and characterize isolates from the environment (soil and water) and monkeys by molecular fingerprint analysis. To date, isolates from the environment rarely infect deep tissues of monkeys. In vitro testing of monkey macrophages demonstrates that cells co-infected with SIV and a common strain of pathogenic M. avium found in our monkey colony produces higher than expected levels of virus. Protein components of our pathogenic strain are being characterized. We have demonstrated that animals infected with SIV and severely immunodeficient can be infected with our pathogenic strain (MavK128) while inoculation with a human strain of M. avium (Serovar 4) fails to infect immunodeficient monkeys. Currently, we have vaccinated four animals with killed M. avium prior to SIV-infection and will assess whether disease is attenuated by vaccination. Future studies will continue to look for promising formulations of M.